APPLICANT'S ABSTRACT: This proposal is for a NIAAA Mentored Clinical Scientist Development Award (KO8) to foster the development of Dr. Laura Jean Bierut's career by supporting her work with Dr. Theodore Reich and Dr. Andrew Heath and other scientists in the field of alcohol abuse research. With this award, the Candidate will be able to further explore the relationship of alcohol dependence and comorbid psychiatric disorders. As the first part of her career development plan, the Candidate proposes to enhance her training through formal course work and independent tutorials in research methodology, statistics, genetic epidemiology, and linkage analysis. These skills will be applied to the analysis of existing data (Australian twin/spouse study, and COGA). As the second part of her career development plan, the Candidate proposes an independent research project to further elucidate the relationship between alcohol dependence and major depressive disorder. The specific aims of the proposal are: I: to measure the association of alcohol dependence and major depressive disorder in a general population sample of Australian twins and their spouses. The effects of assortative mating, environmental influences, secular trends, and associated psychopathology will be examined. Also gender differences in the expression of comorbid alcohol dependence and major depressive disorder will be analyzed. ii: to study the effects of differing diagnostic systems (DSM-IIIR, DSM-IV, ICD-10, Feighner, and Research Diagnostic Criteria) on the comorbidity of alcohol dependence and major depressive disorder in families of probands with alcohol dependence with and without major depressive disorder. iii: to participate in linkage analysis using siblings affected with both alcohol dependence and major depressive disorder and then to compare these results to other analyses of siblings affected with alcohol dependence only and major depressive disorder only. iv: to conduct a prospective study of siblings of alcoholics with a detailed evaluation of comorbid alcohol dependence and major depressive disorder.